{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:11:10Z","timestamp":1791418270675,"version":"4.3.3"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,1,30]],"date-time":"2015-01-30T00:00:00Z","timestamp":1422576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Luminal lipid in the duodenum modulates gastroduodenal functions via the release of gut hormones and mediators such as cholecystokinin and 5\u2010HT.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The effects of luminal short\u2010chain fatty acids (SCFAs) in the foregut are unknown.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Free fatty acid receptors (FFARs) for long\u2010chain fatty acids (LCFAs) and SCFAs are expressed in enteroendocrine cells. SCFA receptors, termed FFA2 and FFA3, are expressed in duodenal enterochromaffin cells and L cells, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Activation of LCFA receptor (FFA1) and presumed FFA3 stimulates duodenal HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion via a glucagon\u2010like peptide (GLP)\u20102 pathway, whereas FFA2 activation induces HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion via muscarinic and 5\u2010HT<jats:sub>4<\/jats:sub> receptor activation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The presence of SCFA sensing in the duodenum with GLP\u20102 and 5\u2010HT signals further supports the hypothesis that luminal SCFA in the foregut may contribute towards the generation of functional symptoms.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Intraduodenal fatty acids (FA) and bacterial overgrowth, which generate short\u2010chain FAs (SCFAs), have been implicated in the generation of functional dyspepsia symptoms. We studied the mechanisms by which luminal SCFA perfusion affects duodenal HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion (DBS), a measure of mucosal neurohumoral activation. Free fatty acid receptor (FFAR) 1 (FFA1), which binds long\u2010chain FA (LCFA), and SCFA receptors FFA2 and FFA3 were immunolocalised to duodenal enteroendocrine cells. FFA3 colocalised with glucagon\u2010like peptide (GLP)\u20101, whereas FFA2 colocalised with 5\u2010HT. Luminal perfusion of the SCFA acetate or propionate increased DBS, enhanced by dipeptidyl peptidase\u2010IV (DPPIV) inhibition, at the same time as increasing GLP\u20102 portal blood concentrations. Acetate\u2010induced DBS was partially inhibited by monocarboxylate\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> exchanger inhibition without affecting GLP\u20102 release, implicating acetate absorption in the partial mediation of DBS. A selective FFA2 agonist dose\u2010dependently increased DBS, unaffected by DPPIV inhibition or by cholecystokinin or 5\u2010HT<jats:sub>3<\/jats:sub> receptor antagonists, but was inhibited by atropine and a 5\u2010HT<jats:sub>4<\/jats:sub> antagonist. By contrast, a selective FFA1 agonist increased DBS accompanied by GLP\u20102 release, enhanced by DPPIV inhibition and inhibited by a GLP\u20102 receptor antagonist. Activation of FFA1 by LCFA and presumably FFA3 by SCFA increased DBS via GLP\u20102 release, whereas FFA2 activation stimulated DBS via muscarinic and 5\u2010HT<jats:sub>4<\/jats:sub> receptor activation. SCFA\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> exchange also appears to be present in the duodenum. The presence of duodenal fatty acid sensing receptors that signal hormone release and possibly signal neural activation may be implicated in the pathogenesis of functional dyspepsia.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.280792","type":"journal-article","created":{"date-parts":[[2014,11,29]],"date-time":"2014-11-29T03:39:55Z","timestamp":1417232395000},"page":"585-599","source":"Crossref","is-referenced-by-count":86,"title":["Short\u2010chain fatty acid sensing in rat duodenum"],"prefix":"10.1113","volume":"593","author":[{"given":"Yasutada","family":"Akiba","sequence":"first","affiliation":[{"name":"Greater Los Angeles Veterans Affairs Healthcare System, 11301 Wilshire Boulevard  Los Angeles CA 90073 USA"},{"name":"Department of Medicine, University of California  Los Angeles CA 90095 USA"},{"name":"Brentwood Biomedical Research Institute  11301 Wilshire Blvd, Los Angeles CA 90073 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